Modern cell biology includes a variety of techniques to manipulate various cells of living organisms in vitro. Of particular interest is a category of cell known as a stem cell. Stem cells are undifferentiated or only partially differentiated cells that have the capability to differentiate into a number of progenitor and mature cell lineages and types. The term “stem cells” can be used to refer to a cell type which is the progenitor of a differentiation cellular lineage in a larger organism, such as hematopoietic stem cell, or can refer to totally undifferentiated stem cells which, at least in theory, have the ability to differentiate into any of the tissues of the body. Stem cells are, at a minimum, pluripotent, meaning that they have the potential to differentiate into many different cell types, and may be totipotent, meaning have the potential to differentiate into any cell type of a mature organism of the species. Stem cell cultures have been developed from a variety of tissue types and from a number of different animals.
Recently, it has become possible to generate, culture and maintain cultures of primate embryonic stem cells, including human and rhesus embryonic stem cells. See, for example, U.S. Pat. No. 5,843,780 and No. 6,200,806 to Thomson. Primate embryonic stem cells are stem cultures created from embryos that survive indefinitely in culture and demonstrate the ability to differentiate into the major tissue types of the primate body. Primate embryonic stem cells can be maintained indefinitely in an undifferentiated state in culture, or can be allowed to start a differentiation process by which various of the cells become committed to one or multiple developmental lineages. Typically, the differentiation of stem cells into different tissue types begins with the creation of embryoid bodies, which causes the stem cells in the embryonic body to begin to differentiate into various cell types.
A more differentiated type of human cell of scientific and research interest is a human trophoblast. A trophoblast is a cell which is a precursor of the cells which participate in the formation of the human placenta. When an embryo begins differentiation, at the stage of a blastocyst, the cells in the inner cell mass are committed to form the cells which will become the embryo, while the outer cells of the blastocyst become committed to participate in the development of the placenta. Trophoblast cells have been isolated before, but they are difficult to isolate and have not been available for research in significant amounts. Mouse trophoblast cell lines have been created from blastocyst and post-implantation trophoblasts. Human trophoblast cell lines have been created from transformed placental cells, but techniques to create cultures of primate trophoblasts from embryonic cells or stem cell lines have not yet been reported. While human embryonic stem cells will spontaneously differentiate into a number of differentiated cell types, including some trophoblast cells, this phenomenon has not led to the creation of useful cultures of trophoblast cells. In fact, mouse embryonic stem cells appear to lack the ability to differentiate into trophoblast, and hence, the supply of trophoblasts has always been extremely limited. A replenishable supply of consistent trophoblast cells would be very useful for many pharmaceutical investigations. In particular, the exploration of contraceptive drugs targeting embryo implantation and therapeutics preventing placenta-related birth defects remain the topics of scientific investigation that can be pursued with more ease provided that a source of primate trophoblasts is available.